Propionibacterium acnes and bacterial resistance

12 Pages·2016·0.21 MB·English

27
Propionibacterium acnes and bacterial Review article
resistance
Propionibacterium acnes e a resistência bacteriana
DOI: http://dx.doi.org/10.5935/scd1984-8773.2015731683
Authors:
Juliane Rocio Neves1
Fábio Francesconi2
ABSTRACT Adilson Costa3
Beatriz de Medeiros Ribeiro4
Propionibacterium acnes (P. acnes) is one of the main microorganisms found on the
Ivonise Follador5
skin. It is predominantly found in hair follicles, prefers anaerobic conditions, preferably Luiz Maurício Costa Almeida6
colonizes the areas with high sebum production, and is the main bacterium involved
1 MSc in Health Sciences. Coordinator, Acne
in the pathogenesis of acne. The indiscriminate use of antibiotics for the treatment of Ambulatory, Dermatolgy Department,
acne vulgaris can result in the development of bacterial resistance. The present article Hospital Regional da Asa Norte - Brasília
(DF), Brazil
is aimed at updating dermatologists with the most current data – from the classifica-
tion to the physiopathogenic mechanisms involved in bacterial resistance to P. acnes 2 PhD in Internal Medicine. Coordinator and
Preceptor, Medical Residency Program
and its possible clinical implications.
in Dermatology, Universidade Federal da
Keywords: Propionibacterium acnes; drug resistance, bacterial; acne vulgaris Bahia (UFBA) - Salvador (BA), Brazil
3 PhD in Dermatology. Researcher, Jack Ar-
biser’s Laboratory, Dermatology Depart-
ment, Emory University School of Medici-
ne - Atlanta (GA), USA
RESU MO
O Propionibacterium acnes (P. acnes) é um dos principais microrganismos observados na pele. 4 MSc in Tropical and Infectious Diseases.
Dermatology Assistant Instructor and
Encontrado predominantemente nos folículos pilosos, prefere condições anaeróbicas, coloniza prefe-
Preceptor, Medical Residency Program in
rencialmente as regiões com alta produção de sebo e é a principal bactéria envolvida na patogênese Dermatology, Universidade Federal do
da acne. O uso indiscriminado de antibióticos para o tratamento da acne vulgar pode causar o Amazonas (Ufam). Coordinator, Medical
Residency Program in Dermatology, Fun-
desenvolvimento de resistência bacteriana. Este artigo tem a intenção de fornecer ao dermatologis- dação de Medicina Tropical Dr. Heitor Viei-
ta os dados mais atuais desde sua classificação até os mecanismos fisiopatogênicos envolvidos na ra Dourado - Manus (AM), Brazil
resistência bacteriana do P. acnes e suas possíveis implicações clínicas.
5 Senior Physician, Head of the Dermatology
Palavras-chave: Propionibacterium acnes; farmacorresistência bacteriana; acne vulgar Department, Hospital de Força Aérea do
Galeão - Rio de Janeiro (RJ), Brazil
6 MSc in Medicine. Dermatology Instructor,
Faculdade de Ciências Médicas de Minas
Gerais. Preceptor, Medical Residency Pro-
gram in Dermatology, Santa Casa de Belo
Horizonte - Belo Horizonte (MG), Brazil
INTRODUCTION Correspondence:
Propionibacterium acnes (P. acnes) is a gram-positive, facul- Dr. Luiz Maurício Costa Almeida
Av. Francisco Sales, 1463/ sala 503 -
tative anaerobic, diphtheroid-type, non-spore forming bacillus.1 Funcionários
This bacterium is part of the skin’s microbiome and has a con- 30140-120 - Belo Horizonte – MG
E-mail: [email protected]
firmed presence in the stratum corneum and pilosebaceous units.2
P. acnes contributes to half of the skin’s microbiome, with Received on: 20/08/2015
an estimated density of 102 to 106 clones per square centimeter.3 Approved on: 14/09/2015
In the skin, its distribution is prevalent in the facial and scalp areas, This study was carried out at the Dermatolo-
and is related to the high concentration of pilosebaceous units in gy Department, Faculdade de Ciências Médi-
cas de Minas Gerais – Belo Horizonte (MG),
these sites.4 It is common in areas rich in eccrine sweat glands and Brazil.
mucous membranes, however it is also present in small amounts in
Financial support: Global Alliance Acne Brazil.
the lower limbs.5 This agent is also part of the microbiome of the
conjunctiva, outer ear, oral cavity, and upper respiratory tract.6 It Conflict of interest: All authors are members of
the Global Alliance Acne Brazil.
can be occasionally commensal in the peripheral lung tissue and
mediastinal lymph nodes.7
Surg Cosmet Dermatol 2015;7(3 Suppl 1):S27-38.
28 Neves JR, Francesconi F, Costa A, Ribeiro BM, Follador I, Almeida LMC
P. acnes was previously called Corynebacterium acnes, in ref- which uses 6-9), it became possible to define the P. acnes’ ribo-
erence to its ability to ferment carbohydrates into propionic acid types (RT), a fingerprint of the restriction fragments of genomic
and light chain fatty acids (LCFA) – substances with known DNA. The analysis of sixty-nine strains allowed for the iden-
antimicrobial activity.8 Lipids and fatty acids, as well as pantoth- tification of the following RTs: 19 RTs1, 5 RTs2, 15 RTs3, 8
enate, nicotinamide acids are the main sources of nutrition for RTs4, 7 RTs5, 4 RTs6, 6 RTs8, four strains of smaller RTs, and
this bacterium, in addition to some other elements such as cobalt one III strain.26
and iron that make up the diet.9, 10 On average, each individual has 3±2 P. acnes ribotypes,
P. acnes is known for contributing to health by inhibiting with three or more clones with no difference in the abundance
the invasion of the skin by common pathogens such as Staphylo- of the bacteria.3 Among the more frequently found ten ribo-
coccus aureus and Streptococcus pyogenes.11 The hydrolyzation of tri- types, RT1, RT2, and RT3 were the most prevalent in patients
glycerides with the release of free fatty acids contributes to the with and without acne. RT4, RT5 (corresponding to the IA-2
acid pH of the skin’s surface, which is another well-known fac- class, which is considered an acne-specific subtype) and RT8
tor for skin protection.12 Fermentation of glycerol has proven to were more prevalent in patients bearing acne. RT6 was found
have in vitro and in vivo probiotic action, suppressing the growth only in healthy patients.3, 26, 27
of the USA 300 methicillin-resistant Staphylococcus aureus, one of Knowledge of the genetic diversity of P. acnes made it
the most prevalent strains in the community.11 possible to understand why a ubiquitous bacterium in humans
The P. acnes genome encodes all the key components for may be directly related to acne in some individuals and still be
the oxidative phosphorylation and has the genes for the cyto- critical to the microbiome balance.24, 28
chrome c oxidase, which ensures its ability to grow in different Genomic and proteomic analyses complement the cur-
metabolic conditions.13-15 Thus, P. acnes is able to “tolerate” expo- rent knowledge when it demonstrates different profiles, with
sure to oxygen for a few hours and survive in vitro for up to eight four described proteomic patterns. These patterns also differ ac-
months under anaerobic conditions.16 Many of its genes have cording to the conditions of the culture medium, with unique
recognized virulence factors, conferring pathogenic potential to patterns in aerobic and anaerobic conditions, suggesting there is
this bacterium.17 influence of the medium on the bacteria.29

P. acnes GENETIC CLASSIFICATION PATHOGENESIS OF P. ACNES – FACTORS OF VIRULENCE
The sub-classification of P. acnes was introduced by John- P. acnes was historically considered an agent of low patho-
son and Cummins with the demonstration of two distinct phe- gen potential, however the current knowledge about these bac-
notypes of this agent (Type I and Type II), based on studies of teria indicates a genetic diversity with different levels of poten-
serum agglutination and analysis of the cell wall sugars. 18 Subse- tial for virulence.26
quently, the phylogenetic analysis of the RecA gene and hemo- In addition to the single loci 1, 2, and 3 found in RT4
lysin/cytotoxin (tly) of P. acnes strains proved different strains of and RT5 (class IA-2) – subtypes associated with acne – a linear
both types.19 Type I was further divided into IA and IB,19, 20 and plasmid might have a role in the physio-pathogenesis of acne.26
Subtype III was described.21 Genetic division of P. acnes based on It is predominantly found in acne lesions.30 Genomic loci seem
multilocus sequence typing technology (MLST), identifies the to be originated from mobile genetic elements that encode vir-
following subtypes: Type I - IA1, IA2, IB, IC or I-1a, I-1b, I-2, ulence genes.31 The RT8 strains of IB-1 class, also related to
Type II and Type III.22-24 acne, have a single genomic island (20kb locus encoding non-ri-
With the sequencing of the P. acnes genome (KPA171202, bosomal peptide synthetases (NRPS), which are possible viru-
IB strain) the knowledge of this bacterium has further ad- lence factors.4
vanced.25 The analysis evidenced a genome of 2.56Mb with 60% The RT2 strain belongs to Class II and is distributed both
GC, encoding 2,333 open reading frames (ORFs), with multiple in acne-bearing and healthy patients; however RT6 strain pre-
products such as sialidases, neuraminidases, endoglycocerami- vails in the latter group.3 The most characteristic genetic feature
dases/ endoglycosidases, lipases, and pore-forming enzymes.25 of these strains is the presence of the clustered regularly interspaced
When 82 strains of P. acnes had their genomes compared, it was short palindromic repeats locus (CRISPR)/Cas)3. The CRISPR/
possible to identify concordance in 88% of the genome (2.2Mb). Cas system provides the bacteria with immunity against viruses
Unique single nucleotidepolymorphisms (SNPs) were identified and plasmids.32, 33 Bacteriophage infections have been associated
in the central region 122,223, with the possibility of using the with the potential pathogenic of bacteria and is also a possible
ribotyping of the gene 16S in the construction of the phyloge- therapeutic agent.34, 35
netic tree of P. acnes having been demonstrated.26 The non-cen- Type II strains have decreased lipase activity, which is re-
tral genome, which is not shared by all strains, corresponds to lated to the virulence of P. acnes.10
0.90Mb and assists in distinguishing between different strains.26 Type III strains are rarely found on the skin’s surface.36
Combining the knowledge of the bacterium’s genome There is a loss of 43kb in the length of the genome with
and the greater ease of use of the technique based on the se- 42ORFs of specific genomic property.26 This subtype is related
quencing of the 16 S rRNA as compared with the MLST tech- to vertebral disc infection.27, 37
nique (the first uses one gene as compared with the second,
Surg Cosmet Dermatol 2015;7(3 Suppl 1):S27-38.
P. acnes and bacterial resistance 29
PATHOGENESIS OF P. ACNES d) Inflammation
a) Influence of the metabolism In patients with acne, P. acnes is capable of activating in-
P. acnes can be related to the initial stage of acne due to nate immunity via toll-like receptor type 2 (TLR2).54 This acti-
the fact that it causes an increase in the lipogenesis originated in vation occurs via cell wall components of the bacterium,55, 56 ex-
sebaceous glands.38 It acts through the action of soluble factors cept for when it is not damaged or inactivated.57 In response to
or direct action with an increase in the production of 15-de- the activation of TLR2, there is production of IL-1a by follicular
oxy-12, 14 -prostaglandin J2 (15d-PGJ2) via the cytochrome P450 keratinocytes,58 (a proven role in the comedogenesis), produc-
with increased triacylglycerol synthesis.38, 39 IGF-1 and IGF-1R tion of nuclear factor kappa-light (NF-kB, primary transcrip-
are a well known target of P. acnes.40 tional factor of fast action) by activated B cells,59 and production
There is also evidence that P. acnes influences the dif- of IL-12 and IL-8 by monocytes.54 When in vitro, P. acnes is capa-
ferentiation of keratinocytes via an increase in transglutaminase ble of inducing the mRNA of the MMP-9 and MMP-1 and the
and cytokeratin,17 and a decrease in the expression levels of cy- expression of MMP-9 (but not MMP-1), through a mechanism
tokeratins 1 and 10.41 Some strains are even capable of increasing dependent on TLR2.48
the involucrin, the expression of mRNA of cytokeratin 6, and The in vitro activation of macrophages is accompanied
decreasing the levels of expression of cytokeratin 6 and 16.41 The by increased expression of the synthase gene induced by nitrous
effect on keratinocyte differentiation suggests it has influence on oxide (inducible nitric oxide synthase - iNOS) and of the cyclo-
the formation of microcomedones.42 oxygenase-2 gene (COX-2), with an increase in nitrous oxide
(NO) and of prostaglandin E (PG E2) through a dose-depen-
2
b) Biofilm dent mechanism.60 This activation was also observed in keratino-
The production of a biofilm by Propionibacterium acnes – a cytes. In the same study there is evidence of the toll-like path-
glycocalyx polymer, which acts as a biological glue – was evi- way, for when TLR-2 are blocked with inhibitory antibodies,
denced by genomic studies.43 The production of the biofilm is the increase in the expression of genes is halted.60
closely related to invasive infections and is considered an import- Innate immunity can also be activated by pattern-recog-
ant factor in these infections, as demonstrated in 93 isolates.44 nition cytoplasmic receptors, and the oligomerization domains,
The production of biofilm can take place in the follicles45 by binding with nucleotides (nucleotide binding oligomerization
and has been reported in patients with acne in whom the sub- domain – NOD).61 These receptors are termed NOD-like re-
stance led to inflammation that was not associated with cellular ceptors (NLR) and assist in the identification of microorgan-
immune response.46 When present in the sebum, this polymer isms and molecules with potential for damaging the cell, such
leads to the adhesion of keratinocytes, contributing to the for- as reactive oxygen species (ROS).15 When activated by direct
mation of comedones. It is believed that this substance has an binding , the NLR forms a multiprotein complex with adapter
influence on the immunogenicity, clinical course, and impact on proteins and pro-caspase-1, and is then termed inflammasome.62
the therapeutic response of acne pictures.43 Four inflammasomes are described as being capable of identify-
ing bacteria: NLRP1, NLRP3, NLRC4 (also known as IPAF)
c) Proteases – all of which belong to the NLR family – and a fourth called
There is evidence suggesting P. acnes has a role in in- AIM2 – that does not belong to this family.63 Their activation
creased expressions of interleukins 1’s and 8’s mRNA, of tu- takes place after the cleavage of pro-caspase-1 active caspase-1,
mor necrosis factor alpha, of human beta defensin beta 2, and of the protease that processes the pro-interleukin 1b and 18 into
metalloproteinases 1, 2, 3, 9 and 13 in keratinocytes by activation mature and active interleukins.22
of proteases, and of proteins activated receptor (protein-activated P. acnes activates the NLRP3 on human monocytes.63 It
receptor 2 PAR-2).47 Metalloproteinases can be related both to has been shown that the release of IL-1b by monocytes depends
the pathophysiology of acne48 and scar formation.49 on the phagocytosis of P. acnes.61 Strains with proven ability to
The Christie, Atkins, Munch-Peterson factor (Camp fac- invade epithelial cells are of type I in 71% of cases.64, 65 IL-1b is
tor) is a secretory protein with co-hemolytic activity and viru- potentially responsible for the induction of in vivo neutrophilic
lence potential against keratinocytes and macrophages that can inflammatory response induced by P. acnes.66 The bacterium can
be encoded by P. acnes.50 Despite being secreted by P. acnes, the induce the formation of caspase-1 in neutrophils, with the gen-
specific role of the Camp factor in the pathogenesis of disorders eration of additional IL-1b and IL-18.67 The activation of the
is still unclear.51 inflammasome can also activate NF-Kb.65 P. acnes also induces
Endogenous porphyrins can be produced by P. acnes with the production of IL-1 in sebocytes.68
a possible influence on perifollicular inflammation by cytotox- P. acnes stimulates the production of genes linked to the
ic effect and the stimulus of interleukin 8 production.52 After Th17 immune response, in addition to stimulating the secre-
the follicle’s rupture and probably by the action of singlet ox- tion of IL-17 by CD4+ lymphocytes. Vitamin A, and vitamin
ygen, the porphyrins can continue their action due to the fact D are capable of inhibiting the Th17 differentiation induced by
they promote the development of cytotoxic substances, such as P. acnes.69
squalene peroxide.53 With the expanding knowledge about the different P.
acnes strains and their influence on innate immunity, the identi-
Surg Cosmet Dermatol 2015;7(3 Suppl 1):S27-38.
30 Neves JR, Francesconi F, Costa A, Ribeiro BM, Follador I, Almeida LMC
fication of the phylogenetic groups tend to occur not only based antibodies against P. acnes,88-90 granuloma based isolation in cul-
on the standard of secreted proteins, but also based on the ability ture, 91 and the complete sequencing of the sarcoidosis bearing
to induce different patterns of immune response.70 Another im- patient’s bacterium’s genome.92 A murine experimental model
portant aspect of the inflammatory cascade induced by P. acnes was capable of inducing sarcoidosis granuloma formation after
is that some are stimulated by dead P. acnes or its components, a the administration of a recombinant protein from active93 or
fact that should be taken into consideration in the acne bearing dead94 P. acnes.94 Considering the studies on the influence of P.
patient’s therapeutic strategy, using substances with bactericidal acnes on sarcoidosis, authors have postulated the hypothesis that
and anti-inflammatory actions.71 a hypersensitivity response, with a change in Th1/Th17 balance
Knowledge of the impact of this bacterium on the im- can generate the sarcoidosis picture.95 In an interesting case re-
mune system has allowed the use of this agent in various im- port that identifies P. acnes in sarcoidosis granuloma, the patient
munomodulatory strategies, especially in veterinary medicine, as was treated with clarithromycin with the complete resolution of
described in the following examples: the inactivated bacteria stim- the condition88.
ulates Th1 and Th2 response in mice;72 it is capable of inducing
antitumor response,73 increasing the resistance against viral and Prostate cancer
parasitic infections, preventing focal segmental glomerulosclerosis; Recent studies relate the chronic inflammatory state with
74 it has antibacterial activity;75-78 in murine model of sepsis it re- prostate carcinogenesis due to DNA damage that leads to tissue
duces the mortality by 50%;79 it is used in a vaccine that improves replication, migration, and angiogenesis.96 There is evidence of
the atopic dermatitis murine model;80 in addition to its use aimed P. acnes in prostate tissue with chronic inflammation,97 verified
at preventing infections81 and preparing vaccines.82 through techniques of monoclonal antibody,98 in situ hybrid-
ization with fluorescence,99 and immunohistochemistry.100 The
Evasion mechanisms infection’s pathway is not yet established, but isolation of P. acnes
After having been phagocytized, P. acnes can survive and in urine samples suggests the urethra is a possible channel.101, 102
persist within macrophages, interfering or blocking the matu- A murine model of chronic prostatic inflammation was possi-
ration pathway of phagosomes.83 P. acnes has an intracellular life ble after transurethral catheterization of P. acnes.103 Categorizing
cycle, offering a possible niche for the survival and spread of the by type, using the MLST technique, demonstrates that prostate
bacteria.83 strains do not have a cutaneous origin, contradicting researchers
who advocate the possibility of contamination during the col-
P. acnes and human diseases lection of prostatectomy material.104 Vimentin appears to be a
P. acnes has a proven role in acne, however its importance key determinant factor for prostatic tissue invasion.105 Another
in other diseases is underestimated. study correlates P. acnes’ titles with prostate cancer.106
With the ability of growing in medium with diverse
oxygenation conditions (in particular in anaerobic settings), of Infection of orthopedic prostheses
surviving intracellularly in macrophages with the potential to P. acnes is one of the agents that causes shoulder prosthesis
generate inflammation and producing biofilm, P. acnes can be infection most frequently (second only to S. aureus).107 Despite
transferred from its habitat (e.g. the skin’s microbiome) to deeper the small number of the sample, the analysis of 22 shoulder pros-
tissues, and with the ability to survive and present pathogenic thetic infection isolates led to the conclusion that the hemolyt-
potential.44 In addition to direct contamination through the skin, ic phenotype was the one most associated in this case.108 This
infection by P. acnes may result from transient bacteremia.84 infection’s prevalence varies from 3.9% to 15.4% and delayed
Infections by this bacterium usually have an indolent diagnosis can have an impact on the success of the procedure,
course and are difficult to diagnose for it is a common bacteri- with loss of the prosthesis, chronic pain, exudate and sepsis hav-
um and differentiating contaminations from infections is always ing been described.109 Spinal prosthetic infections are also related
a challenge – nevertheless the formation of biofilm is used to to P. acnes, with an incidence of 0.2%, however possibly reaching
differentiate these two clinical situations.44 In a study with 522 12.0% depending on the used instrumentation.110-112
patients, clinically significant bacteremia of P. acnes occurred in
3.5% of cases, of which 55.6% were classified as nosocomial, Endocarditis
33.3% had a history of previous invasive procedure and 5.9% Endocarditis caused by P. acnes is rare and is related to
mortality.85 heart valve prostheses.113, 114 There are reports of cases that on-
set after invasive procedures.85 Due to the subacute oligosymp-
Sarcoidosis tomatic development, diagnosis is often delayed, entailing valve
Sarcoidosis is a systemic granulomatous disorder that af- and perivalvar destruction or abscess formation, with mortality
fects individuals with genetic susceptibility after exposure to a rates reaching roughly 18.7%.115 Little is known about the ideal
particular environmental stimulus, with Propionibacterium acnes treatment, and surgery is commonly indicated with an aim at
being a proven cause.86 The correlation between the bacterium draining the abscess or replacing the valve.115
and sarcoidosis granuloma was demonstrated by techniques of
in situ hybridization,87 immunohistochemistry with monoclonal
Surg Cosmet Dermatol 2015;7(3 Suppl 1):S27-38.
P. acnes and bacterial resistance 31
Central nervous system infection rect tissular visualization techniques, such as the Fish technique,
P. acnes is related to post-operative infections of the cen- immunofluorescence microscopy and immunohistochemical
tral nervous system, and among common procedures are the use techniques.149
of shunts, bone grafts, craniotomy, abscess drainage, and rare de-
scriptions of meningitis cases with no previous history of proce- Antibiotic resistance by Propionibacterium acnes
dure (8 reported cases).116-119 In half of the cases, symptoms may The first documented antibiotic resistance by P. acnes was
appear acutely within seven days or subacutely within 14 weeks linked to erythromycin.150 The known mechanisms of resistance
in the other half, on average. Symptoms are those deemed classic are: specific mutations to the genes that encode the ribosom-
for meningitis, with a cerebrospinal fluid (CSF) profile corre- al RNA, single mutation in the 16S rRNA (1058G>C) gene,
sponding to that of the aseptic meningitis with mononuclear mutations in the gene 23S rRNA with four recognized pheno-
pleocytosis.19 Based on reports, penicillin G, chloramphenicol typic groups (Group I: 2058A> G, Group II: presence of RNA
or vancomycin are used with favorable results.120 Optic nerve methylase erm(X) gene in a mobile genetic element, Group III:
neuritis121 and abscess formation are described complications.120 2057G> A; Group IV: A2059A> G) and mediated erm(X) resis-
tance.151-152 Resistance to rifampicin is associated with a punc-
Other infections tual mutation in the rpoB gene’s Clusters I and II, and can be
Breast implant infection,17, 122 acute post-traumatic en- prevented if associated with levofloxacin, clindamycin, and pen-
dophthalmitis,123 discitis and spondylodiscitis,124-130 pericardi- icillin G153 (Chart 1).
tis,131 aortic stent endarteritis,132, 133 prosthetic eye infection,134 Antibiotic resistance by P. acnes is better studied in acne
osteomyelitis,135, 136 surgical wound infection,137 endodontic in- patients. The most significant resistance profiles for the treat-
fection138 and keratitis.139 ment of acne are associated with specific strains of bacteria, in
particular ST3 clone, which has worldwide distribution.3, 22 The
Related dermatological conditions ribotypes that are more frequently related to resistance are RT4
Progressive macular hypomelanosis of the trunk,140-142 al- and RT5.3 An individual can host a complex population of P.
opecia143 and Sapho syndrome.144 acnes, with a variable number of clones from one to six, which
have different pathogen potential and different resistance pat-
P. acnes diagnosis terns, issues that directly impact the difficulty in acne treatment.
Despite the bacterium having aerotolerant characteris- 154 In addition to having the bacteria, a person can transmit the
tics, the diagnosis of P. acnes should be performed in a culture different clones, and thus resistant bacteria can be spread in the
medium with anaerobic conditions – thioglycolate is the rou- population.155
tinely used culture medium.145 When enriched, this culture me-
dium has a low redox potential and assists in the growth of the
microorganism145.
There should be a systematic subculture on agar plates Chart 1: Mechanisms of bacterial resistance to antibiotics
even in the absence of turbidity.146 The optimum temperature
Mutation Resistance
for growth is 37ºC, and the duration of inoculation should be
continued for at least 14 days.147 On the other hand, the culture Specific mutation in the gene 165 Tetracyclines
duration should not be too long, for the probability of contam- rRNA (1058G>G)
ination by growth of bacteria originating from the normal flora Specific mutation in the gene 23s MSL Antibiotics (macro-
would increase – as a result the maximum waiting period has rRNA (2058A>G) lide-streptogramin B-lyncos-
not been established yet.147 The interpretation of cultures should amide, including erythromycin
be performed with caution, especially if there is only a single and clindamycin)
medium. For greater reliability of the result, growth should be Presence of the gene RNA methylase
observed in more than one culture medium, always in light of erm (X)
the correlated patient’s clinical data and, where possible, of other Specific mutation in the gene 23s
diagnostic methods, such as histology and molecular diagnostics. rRNA (2057G>A)
146 Fluorescence with in situ hybridization (Fish) is a technique
Specific mutation in the gene 23s
with potential use in blood cultures. It showed 95% sensitivity
rRNA (A2059A>G)
and 100% specificity in the diagnosis of infection by P. acnes.148
For the isolation and identification of P. acnes, attention Specific mutation in the gene 23s Resistance to erythromycin and
should be paid to the collection methodology, for different tech- rRNA (2058A>T) clindamycin
niques will demonstrate anatomically distinct populations: swab Specific mutation in the gene 23s
and scraping are used to identify the more superficial bacteria; rRNA (2058A>C)
the use of tape with cyanoacrylate targets superficial and infun-
Specific mutation in the gene rpoB Rifampicin
dibular populations; the punch evidences deeper follicular pop-
gene
ulations and can be used in biofilm research; finally there are di-
Surg Cosmet Dermatol 2015;7(3 Suppl 1):S27-38.
32 Neves JR, Francesconi F, Costa A, Ribeiro BM, Follador I, Almeida LMC
Table 1 : Percentage of P. acnes resistant to antibiotics, isolated in patients with acnes
Countries Clindamycin Erythromycin Oxytetracycline Doxycycline
Spain (2003) 91 91 5 ______
USA (1983) 79 81 63 57
Greece (2003) 75 75 7 _____
Egypt (2012) 65 48 18 6
Italy (2003) 58 58 - ______
UK (2003) 55,5 55,5 26,4 _______
Hong Kong (2013) 53,5 20,9 16,3 16,3
Sweden (2003) 45 45 15 ______
Hungary (2003) 45 45 - ________
Northern Mexico (2010) 36 46 14 ______
France (2010) __________ 75,1 9,5 9,5
Chile (2013) 7,5 12,5 _________ _______
Colombia (2013) 15 35 8 9
South Korea (2012) 30 26,7 ________ ________
Percentages of P. acnes resistant to antibiotics, isolated from acne patients (based on the article: “Antibiotic stewardship in dermatology: limiting use in acne.” Eur. J. Dermatol. 2014. Authorized by Dr.
Brigitte Dreno).
Percentages of P. acnes resistant to antibiotics, isolated an 82% resistance to azithromycin, 68% resistance to trimetho-
from acne patients (based on the article: “Antibiotic stewardship prim-sulfamethoxazole, and 46% resistance to erythromycin.162
in dermatology: limiting use in acne.” Eur. J. Dermatol. 2014. Elsewhere, in Hong Kong, 54.8% of strains were resis-
Authorized by Dr. Brigitte Dreno). tant (53.5% to clindamycin, 20.9% to erythromycin, 16.3% to
There has been an increasing number of cases of antibi- tetracycline, 16.3% to doxycycline and 16.3% to minocycline),
otic-resistance by P. acnes over the years: in the UK, the resistance with an 11.6% cross-resistance between clindamycin and eryth-
rate increased from 34.5% in 1991 to 55.5% in 2000;156 94% of romycin, and 16.4% of multiple resistors.163 In Egypt, resistance
the isolates in Spain and 51% from the isolates in Hungary were to clindamycin was identified in 66.3%, to erythromycin in 49%,
resistant to at least one antibiotic.155 The highest resistance rates to oxytetracycline in 26.5%, to doxycycline in 16.3%, and to
are related to erythromycin, with cross-resistance to clindamy- azithromycin in 9.2%.164 (Table 1).
cin. The lowest rates are linked to tetracyclines.157, 158 In Australia, growth in the P. acnes resistance rate was not
The evaluation of 114 isolates in Denmark (72 acne observed between 1997-1998 and 2007.165 Prior use of antibiotics
bearing and 42 healthy patients) showed 34% of antibiotic re- (oral or local) was considered a risk factor for resistance, and the
sistance by P. acnes, with 15.8% resistance to clindamycin, 8.8% use of retinoids, despite its decreasing effect in the growth rate of
resistance to erythromycin, and 9.6% resistance to tetracycline, P. acnes, did not influence the incidence of resistant strains.165
with 39 patients having been affected: 25 acne bearing patients A European study of 304 isolates of P. acnes from 13 lab-
who had the highest proportion of isolates with resistance to oratories in 13 different countries tested six antibiotics.166 Blood
tetracycline.154 In Japan, the rate of resistance to macrolides was was the most common source, followed by skin infections, in
4% between 1994 and 1995, however it became much higher soft tissue and abdominal infection.166 Of the isolates, 2.6% were
and related to the erm(X) gene in 2008.159 resistant to tetracycline, 15.1% to clindamycin, and 17.1% to
Data published in Latin America show a resistance ra- erythromycin, without descriptions of resistance to linezolid,
tio of 33.7% in Chile: 26.3% to trimethoprim-sulfamethox- benzathine penicillin, and vancomycin.166 There was a variation
azole, 12.5% to erythromycin, and 7.5% to clindamycin, with in the resistance profile among countries, with 83% in Croatia,
a total cross-resistance between clindamycin and erythromy- 60% in Italy, and none in Norway, with blood isolates showing a
cin, and 40% cross-resistance between erythromycin and tri- prevalence among the resistant ones.166
methoprim-sulfamethoxazole, without identifying resistance to As P. acnes has a low susceptibility to cephalosporins, use
tetracycline and doxycycline.160 The main risk factors for the of antibiotic prophylaxis in surgical procedures (where this bac-
occurrence of resistance were: older age, previous use of top- terium is an important source of post-operative complications)
ical antibiotic and, in the case of trimethoprim-sulfamethox- should be revised.167
azole, the severity of the acne.160 In Colombia, there were 35% In cases of severe infections caused by P. acnes, drugs with
of strains resistant to erythromycin, 15% to clindamycin, 9% to the possibility of resistance cannot be used, and surgical proce-
doxycycline, 8% to tetracycline and 1% to minocycline, with dures should be associated with clinical treatment, with a pref-
12% cross-resistance between erythromycin and clindamycin, erence – when in combination – for using crystalline penicillin,
6% between doxycycline and tetracycline, with previous use of vancomycin, daptomycin, and rifampicin due to their effect on
antibiotics being the main risk factor.161 In Mexico there was the biofilm.166, 168, 169 l
Surg Cosmet Dermatol 2015;7(3 Suppl 1):S27-38.
P. acnes and bacterial resistance 33
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